Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers.

BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. RESULTS: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

DSM-5 Update in Psychodermatology.

Up to a third of dermatology outpatients have a significant psychiatric issue complicating their skin complaint. Although the ideal would frequently involve psychiatric assessment, those with comorbid mental illness often refuse psychiatric referral. As a result, it is imperative that dermatologists be mindful of psychiatric comorbidity in their patients and comfortable with the fundamentals of psychodermatologic diagnosis and therapy. This update summarizes current concepts, relevance, and therapeutics in psychodermatology, including aspects pertinent to depression, anxiety, obsessive-compulsive, impulse-control, and delusional disorders as described in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5, published in 2013 by the American Psychiatric Association).

Factor analysis of the Chinese version of the Autism Spectrum Quotient 10 and its association with schizotypal traits in adolescents and young adults in Hong Kong.

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.

Host-dependent effects of the 3' untranslated region of turnip crinkle virus RNA on accumulation in Hibiscus and Arabidopsis.

Li W., Wong S-M, Journal of General Virology (2007), 88, part 2, pp. 680­687.The authors regret to inform the readers of Journal of General Virology that honest errors were made in the preparation of Fig. 1(c), Fig. 2 and Fig. 3(b) (the rRNA controls were either missing or placed wrongly), such that the findings as presented are deemed unreliable. While the authors stand by the conclusions of the paper, there is currently no editorial mechanism to review the errors. The authors are currently repeating the experiments and will resubmit the paper to Journal of General Virology in due course, but agree to retract the paper at this time, and they regret any inconvenience caused to the readers of the journal.

Gabapentin for the treatment of carpal tunnel syndrome: a randomized controlled trial.

OBJECTIVE: Based on its efficacy in treating neuropathic pain, gabapentin may be effective for the treatment of carpal tunnel syndrome (CTS). The purpose of this study was to evaluate the efficacy of gabapentin for symptom relief in CTS. METHODS: We conducted a randomized, double-blinded, placebo-controlled trial recruiting patients with newly diagnosed idiopathic CTS of more than a period of three months. Diagnosis was based on characteristic symptoms with electrophysiological confirmation. Patients were randomly assigned to an active group receiving gabapentin (starting dose 300 mg once daily to a target of 900 mg daily) or a placebo group. Primary end-point was the global symptom score (GSS), which was measured at baseline, two, and eight weeks. RESULTS: There was no significant difference in baseline variables between the two treatment groups. Hundred and forty patients were enrolled in the study, of whom 71 were randomly assigned to gabapentin group and 69 assigned to placebo group. Both gabapentin and placebo produced significant improvement in symptoms at two and eight weeks. The GSS at 2 and 8 weeks was 16.4 (SD 9.4) and 13.4 (SD 9.7), respectively, in the active group versus 14.9 (SD 9.0) and 12.5 (SD 8.9) in the control group (P < 0.01). But by eight weeks, the mean reduction in symptom severity of patients on gabapentin [-10.4 (SD 10.8)] was not significant when compared with placebo [-8.7 (SD 8.1), P < 0.39]. Adverse events were not severe and included dizziness, somnolence, and headache. CONCLUSIONS: Gabapentin did not produce a significant reduction in symptom severity compared with placebo over an eight-week period.

Plastocyanin transit peptide interacts with Potato virus X coat protein, while silencing of plastocyanin reduces coat protein accumulation in chloroplasts and symptom severity in host plants.

Potato virus X coat protein (PVXCP) is, through communication with host proteins, involved in processes such as virus movement and symptom development. Here, we report that PVXCP also interacts with the precursor of plastocyanin, a protein involved in photosynthesis, both in vitro and in vivo. Yeast two-hybrid analysis indicated that PVXCP interacted with only the plastocyanin transit peptide. In subsequent bimolecular fluorescence complementation assays, both proteins were collocated within chloroplasts. Western blot analyses of chloroplast fractions showed that PVXCP could be detected in the envelope, stroma, and lumen fractions. Transmission electron microscopy demonstrated that grana were dilated in PVX-infected Nicotiana benthamiana. Furthermore, virus-induced gene silencing of plastocyanin by prior infection of N. benthamiana using a Tobacco rattle virus vector reduced the severity of symptoms that developed following subsequent PVX infection as well as the accumulation of PVXCP in isolated chloroplasts. However, PVXCP could not be detected in pea chloroplasts in an in vitro re-uptake assay using the plastocyanin precursor protein. Taken together, these data suggest that PVXCP interacts with the plastocyanin precursor protein and that silencing the expression of this protein leads to reduced PVXCP accumulation in chloroplasts and ameliorates symptom severity in host plants.

Fetal biometry in ethnic Chinese: biparietal diameter, head circumference, abdominal circumference and femur length.

OBJECTIVES: To construct new reference charts and equations for fetal biometry in the Hong Kong ethnic Chinese population, and to compare them with existing references from different populations. METHODS: This was a prospective observational study involving 709 women with singleton pregnancies and confirmed gestational age. For the purposes of this study, each woman was scanned once only, between 12 and 40 completed weeks of gestation, and the following fetal biometric measurements were recorded: biparietal diameter, head circumference, abdominal circumference and femur length. For each measurement, regression models were fitted to estimate the mean and SD at each gestational age. For comparison, the fetal biometric measurements of other populations at each gestation were expressed as Z-scores calculated with our reference equations. Results were presented graphically across the different gestational ages to allow visual comparison. RESULTS: New charts and reference equations are reported in this Hong Kong Chinese population for fetal outer-inner and outer-outer biparietal diameter, head circumference, abdominal circumference and femur length. Equations for dating of pregnancy are presented. Our charts were very similar to those of the Singaporean population for most parameters. The main difference in our fetal biometric measurements compared with those of the UK and French populations was in FL. CONCLUSIONS: Our new set of reference centiles for fetal biometric measurements and equations for dating of pregnancy in a Hong Kong Chinese population are ready for clinical use and research in appropriate ethnic Chinese groups.

First Report of Phytoplasma Infection of Grasses in Singapore.

In September of 2005, patches of Cynodon dactylon showing symptoms of bleached leaves were first observed in an open field in Singapore. Samples were collected from this site, from which total DNA was extracted with a Qiagen DNeasy kit (Catalog No 69104) and analyzed for phytoplasma DNA by a PCR assay with phytoplasma universal primer pairs P1/PTint (3). Resulting PCR products were each diluted 1:30 with sterilized distilled water and used in nested PCR with primer pair R16F2n and R16R2 (1). Twenty-five C. dactylon samples were assessed by this means, of which eight of eight with bleached leaves and four of seventeen symptomless samples tested positive. Widened disease surveillance identified the grasses, Axonopus compressus and Paspalum conjugatum, with similar bleached leaf symptoms in December 2006 and May 2007, respectively. Twenty-three of fifty-three A. compressus and six of twenty P. conjugatum samples were detected as positive for phytoplasma infection with the above PCR methods. A comparative analysis of sequences derived from the three grass hosts determined that the phytoplasma infecting C. dactylon (Genbank Accession No. EU234510) was most similar (>99%) to 'Candidatus Phytoplasma cynodontis' (GenBank Accession No. AB052871.1), whereas those detected in A. compressus (Genbank Accession No. EU234511) and P. conjugatum (Genbank Accession No. EU234512) were most similar (>99%) to the Brachiaria white leaf phytoplasma (GenBank Accession No. AB052872.1) (2). To our knowledge, this is the first report of phytoplasmas in C. dactylon, A. compressus, and P. conjugatum in Singapore. References: (1) I. M. Lee et al. Int. J. Syst. Evol. Microbiol. 48:1153, 1998. (2) C. Marcone et al. Int. J. Syst. Evol. Microbiol. 54:1077, 2004. (3) C. D. Smart et al. Appl. Environ. Microbiol. 62:2988, 1996.

On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease.

BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 ± 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 ×10-2 and for parenchymal diffusivity from 7.20 to 9.11 × 10-4 mm2/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were <3.70% in normal-appearing tissue and <9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 × 10-2 and 0.10 to 0.37 × 10-4 mm2/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.

[Impact of maternal risky behaviors on the behaviors of children born to adolescent and young mothers].

Objective: To examine the impact of maternal risky behaviors on the behaviors of children born to adolescent and young mothers. Methods: Adolescents and young Chinese mothers were recruited from an integrated young mother supportive program in Hong Kong between January and June 2015. Eligible mothers were asked to complete a questionnaire on their sociodemographic characteristics and history of risky behavior as well as their children's behaviors. Multiple regression analyses were conducted to explore the association between maternal risky behaviors and their children's behaviors. Results: Among 201 respondents, there were 187 (93.0%) ex-drinkers, 136 (67.7%) ex-smokers, and 83 (41.3%) ex-addicts. Compared to the reference group, children of mothers with drug use behaviors were more likely to have abnormal SDQ total difficulties scores (odds ratio 2.60, P=0.01), those of ex-drinking mothers had more behavioral difficulties and more conduct problems (B=3.82 and 1.37, P both=0.01) and those of ex-smoking mothers had more conduct problems (B=0.74, P=0.01) after adjustment for confounders. Children of active drug-taking mothers also had more emotional symptoms (B=1.77, P=0.04) and hyperactivity/inattention problems (B=2.14, P=0.03). Conclusion: The history of mother's risky behavior was significantly associated with the behavioral problems of the children.

Hibiscus chlorotic ringspot virus p27 and its isoforms affect symptom expression and potentiate virus movement in kenaf (Hibiscus cannabinus L.).

Hibiscus chlorotic ringspot virus (HCRSV), a member of the genus Carmovirus, encodes p27 (27-kDa protein) and two other in-frame isoforms (p25 and p22.5) that are coterminal at the carboxyl end. Only p27, which initiates at the 2570CUG codon, was detected in transfected kenaf (Hibiscus cannabinus L.) protoplasts through fusion to a Flag tag at either its N or C terminus. Subcellular localization of a p27-green fluorescent fusion protein in kenaf epidermal cells showed that it was localized to membrane structures close to cell walls. To study the functions of these proteins, a number of start codon mutants and premature translation termination mutants were constructed. Phenotypic differences were observed between the wild-type virus and these mutants during infection. Infectivity assays on plants indicated that p27 is a determinant of symptom severity. Without p25, appearance of symptoms on systemically infected kenaf leaves was delayed by 4 to 8 days. In a timecourse analysis, Western blot assays revealed that the delay corresponded to retardation in virus systemic movement, which suggested that p25 is probably involved in virus systemic movement. Mutations disrupting expression of p22.5 did not affect symptoms or virus movement.

Enhancement of the dissolution rate and oral absorption of a poorly water soluble drug by formation of surfactant-containing microparticles.

The slow dissolution rate exhibited by poorly water-soluble drugs is a major challenge in the drug development process. Following oral administration, drugs with slow dissolution rates generally show erratic and incomplete absorption which may lead to therapeutic failure. The aim of this study was to improve the dissolution rate and subsequently the oral absorption and bioavailability of a model poorly water-soluble drug. Microparticles containing the model drug (griseofulvin) were produced by spray drying the drug in the absence/presence of a hydrophilic surfactant. Poloxamer 407 was chosen as the hydrophilic surfactant to improve the particle wetting and hence the dissolution rate. The spray dried particles were characterized and in vitro dissolution studies and in vivo absorption studies were carried out. The results obtained showed that the dissolution rate and absolute oral bioavailability of the spray dried griseofulvin/Poloxamer 407 particles were significantly increased compared to the control. Although spray drying griseofulvin alone increased the drug's in vitro dissolution rate, no significant improvement was seen in the absolute oral bioavailability when compared to the control. Therefore, it is believed that the better wetting characteristics conferred by the hydrophilic surfactant was responsible for the enhanced dissolution rate and absolute oral bioavailability of the model drug.

Fast-dissolving microparticles fail to show improved oral bioavailability.

Oral dosage forms are the preferred means of delivering drugs for systemic absorption. However, development problems occur for drugs with poor water solubility and/or gastrointestinal permeability. It is generally believed that the in-vivo bioavailability of poorly water-soluble drugs from Class II of the Biopharmaceutics Classification System can be improved by increasing the dissolution rate. We have attempted to increase the in-vivo oral bioavailability of a model Class II drug (griseofulvin) by preparing rapidly-dissolving particles. The solvent-diffusion method was used to prepare particles with hydrophilic surfactants (Brij 76/Tween 80 surfactant blend) and in-vivo studies were conducted in rats. The griseofulvin particles produced were bipyramidal in habit with a particle size of 2.18 +/- 0.12 microm; they contained crystalline drug and a relatively large proportion (12% w/w) of hydrophilic surfactant. The latter and the small particle size ensured rapid particle dispersion and dissolution in-vitro. Thus, within 30 min of the in-vitro dissolution test, the bipyramidal particles had released approximately 70% of drug compared with approximately 10% from the starting material (particle size 12.61 +/- 1.11 microm). However, the rapid and increased drug dissolution in-vitro was not translated to rapid and enhanced absorption in-vivo, and the oral bioavailability of the model drug was found to be the same from the control and from the bipyramidal particles. The poor in-vivo performance of the bipyramidal particles showed that although the dissolution rate of a Class II drug is thought to be a good indicator of its in-vivo bioavailability, this is not always the case.

Inhibition of liver prenyltransferase by alkyl phosphonates and phosphonophosphates.

n-Pentyl and n-decyl phosphonate and the corresponding phosphonophosphates were found to inhibit cholesterol synthesis from mevalonate in the 10000 X g supernatants of liver homogenates and the synthesis of farnesyl pyrophosphate from geranyl and isopentenyl pyrophosphate by purified liver prenyltransferase. Kinetic analysis of the inhibition of prenyltransferase showed that the phosphonates and the phosphonophosphates interacted with two forms, or two sites, of the enzyme. The order of increasing potency was C5-phosphonate less than C10-phosphonate less than C5-phosphonophosphate less than C10-phosphonophosphate. The phosphonophosphates were at least ten times stronger inhibitors than the phosphonates.

Carbachol increases basolateral K+ conductance in T84 cells. Simultaneous measurements of cell [Ca] and gK explore calcium's role.

To explore the role of calcium in mediating the action of carbachol in chloride-secreting epithelia, we simultaneously measured intracellular free [Ca] ([Ca]i) and the potassium conductance (gK) of the basolateral membrane in T84 cells grown on collagen-coated filters. [Ca]i was measured with fura-2 and fluorescence microscopy and expressed as a relative value ([Ca]'i) normalized to control. To assess changes in basolateral gK, we measured the short circuit current (Isc) in the presence of luminal amphotericin and a transepithelial mucosa-to-serosa K+ gradient (Germann, W. J., M. E. Lowy, S. A. Ernst, and D. C. Dawson. 1986. J. Gen. Physiol. 88:237-251). Treatment of the monolayers with carbachol resulted in a parallel increase and then decrease in [Ca]'i and gK. The carbachol-induced changes in gK appeared to be dependent on the increase in [Ca]i because stimulation of gK was significantly diminished when the hormone-induced increase in [Ca]'i was blunted, either by loading the cells with BAPTA or by reducing the extracellular [Ca]. The carbachol-stimulated increase in gK appeared to be the direct result of the increase in steady-state [Ca]'i. The changes in gK and [Ca]'i after stimulation with carbachol were correlated and ionomycin also increased gK and [Ca]'i in a parallel manner. The carbachol-induced delta gK per delta[Ca]'i, however, was greater than that after ionomycin. Because ionomycin and carbachol appear to open the same channel, a conclusion based on inhibitor and selectivity experiments, carbachol may have a second action that amplifies the effect of calcium on gK.

Developing a measure to evaluate a positive youth development program for Native Hawaiians: the Hui Malama o ke Kai rubrics of Hawaiian values.

OBJECTIVE: This study introduces the rubrics of Native Hawaiian values developed to measure youth knowledge and understanding of indigenous values along with 8 other tools to evaluate Hui Malama o ke Kai (HMK), a culturally relevant, positive youth development, after-school program in a Native Hawaiian community. Findings from our efforts to validate the rubrics tool, as an evaluation measure, using triangulation are presented. METHODS: Evaluation tools were modified through community input and measured youth risk and protective factors, including knowledge and practice of Hawaiian values. Validity and reliability of the tools were tested by analyzing internal consistency, intraclass correlations, and triangulating data sources. RESULTS: Corroboration of results from the different data sources indicated convergent validity of measures to evaluate youth understanding and practice of Hawaiian values. CONCLUSIONS: This community-focused approach to evaluation demonstrates how multiple evaluation instruments may reliably evaluate a program.

Sequence of the cDNA encoding human GP-2, the major membrane protein in the secretory granule of the exocrine pancreas.

GP-2 is the major membrane protein in the pancreatic secretory granule of the exocrine pancreas. The nucleotide sequence of the human GP-2 gene was determined from cDNA clones isolated from a lambda gt11 pancreatic library.

YKE2, a yeast nuclear gene encoding a protein showing homology to mouse KE2 and containing a putative leucine-zipper motif.

The nucleotide sequence of YKE2, a yeast nuclear gene, has been determined. The deduced YKE2 protein has 114 amino acids (12 kDa), shows significant homology with the murine KE2 and contains a putative Leu-zipper motif characteristic of a group of DNA-binding proteins [Landschulz et al., Science 240 (1988) 1759-1764]. Strains in which YKE2 has been disrupted show normal cell growth in glucose and galactose media over the temperature range of 16 to 40 degrees C. Disrupted strains also display normal mating and sporulation abilities. Northern analysis revealed that the transcription of YKE2 is unresponsive to catabolite repression by glucose.

The complete sequence of a Singapore isolate of odontoglossum ringspot virus and comparison with other tobamoviruses.

The complete sequence of a Singapore isolate of odontoglossum ringspot virus (ORSV-S1) comprises 6609 nucleotides (nt) and four open reading frames (ORFs 1 to 4). The 126/183-kDa RNA-dependent RNA polymerase (RdRp), 33-kDa movement protein (MP) and 18-kDa coat protein (CP) cistrons are located at nt 63-3401/4901, 4807-5718, and 5721-6197 on the genome, respectively. The 5' UTR contains three copies of an 8-base direct repeat and (CAA)n motifs. Characteristic tRNA-like structure and three consecutive homologous regions were present in the 3' UTR. The genomic RNA and MP of ORSV-S1 are one of the longest among all members of the TOV group. Phylogenetic analysis of all four genes indicates evolutionary divergence, but within each gene there are some degrees of evolutionary convergence. The conserved amino acid sequences in the MP can be used for the classification of tobamoviruses.

Local vs systemic corticosteroids in the treatment of carpal tunnel syndrome.

The authors compared the effectiveness of low-dose, short-term oral prednisolone vs local methylprednisolone injection in a prospective, double-blinded, parallel treatment study of carpal tunnel syndrome (CTS). A single injection of 15 mg methylprednisolone resulted in significant improvement in global symptom scores over a 12-week period. This study demonstrated the superiority of local steroid injection to oral steroid in the treatment of CTS.